1. Santina Snow Rogers Lab MDI Biological Laboratory
The role of specific tissues in coordinating changes in growth, longevity and resilience to stress in response to reduced mRNA translation in C. elegans
Santina Snow
Rogers Lab
MDI Biological Laboratory

2. Maintaining protein balance
folding
degradation
synthesis

3. Maintaining protein balance
unfolded protein
refolding
degradation
aggregation
(disease?)

4. Maintaining protein balance
folding
degradation
synthesis

5. Translation initiation as a point of proteostatic regulation.
synthesis
Tight knit regulation
Links nutrient availability and translation
Reduce and redirect

6. eIF4G (ifg-1) is an essential translation component and longevity factor.
Eukaryotic Initiation Factors (eIFs)
eIF4G
Highly conserved
Essential
Regulatory factor
Adapted from Montero et al (2015)
Control
eIF4G
Unpublished images by Amber Howard, Ph.D.

7. eIF4G (ifg-1) is an essential translation component and longevity factor.
log2(fold change)
ANOVA with post-hoc Tukey; *p < 0.05.
Adapted from Howard et al (2016)
Snow et. al. manuscript in preparation

8. Lowering translation activates the cytoprotective heat shock response.
Part 1 Summary
Lowering translation activates the cytoprotective heat shock response.

9. Tissues need to communicate to maintain homeostasis and viability.
Too much glucose! RELEASE THE INSULIN!
Brace yourself, insulin is coming…

10. Experimental Approach and Aims
Body Wall Muscle
C. elegans mutants express RNAi machinery in only tissue of interest
Feed animals bacteria containing ifg-1 dsRNA
Reduce translation in tissue of interest at desired life stage
Intestine
Hypodermis
Neurons
Germline
Spermatheca
Adapted image from Amber Howard, PhD

11. Reduced translation (ifg-1) in the muscle enhances fertility…
Snow et. al. manuscript in preparation
n=8-19; Unpaired two tailed t-test with Welch’s correction (*p<0.05, **p < 0.01, ***p < 0.001, **** p < )

12. …through increased spermatogenesis.
Snow et. al. manuscript in preparation
n=20-70; Unpaired two tailed t-test with Welch’s correction (**p < 0.01, ***p < 0.001, **** p < )

13. Reduced translation (ifg-1) in muscle accelerates development.
***
Snow et. al. manuscript in preparation
Error bars are SEM; n=5-16; Student’s unpaired two tailed t-test (# p < 0.05, *p < 0.01, **p < 0.001, *** p < )

14. Reduced translation (ifg-1) lifespan extension is tissue dependent.
32%
16%
11% 0%
1.4%
19%
Snow et. al. manuscript in preparation
Lifespans were repeated at least three times; n= per lifespan.

15. Unfolded proteins accumulate with age, disrupting proteostasis
refolding
degradation
aggregation
(disease?)

16. Snow et. al. manuscript in preparation
Tissue-specific reduced translation (ifg-1) possibly aids in regaining proteostasis following acute heat stress.
Days of adulthood 1 2 3 4 5 6 7 8 9 10 11 12
20°C
35°C 1 2 3 4 5
Days post heat stress
Snow et. al. manuscript in preparation

17. Parkinson’s disease model as proteotoxic stress in C. elegans
Muscle specific
promoter
α-synuclein

18. Snow et. al. manuscript in preparation
Reduced translation (ifg-1) in distal tissues can enhance resistance to muscular α-synuclein proteotoxicity.
****
Wild Type
Germline
**** **
Muscle
Hypodermis
****
Snow et. al. manuscript in preparation
Paralysis assays were repeated at least three times; n= per assay; Mantel-Cox log rank test (** p < 0.01, **** p < )

19. The effect of reduced translation is tissue-specific
Part 2 Summary
The effect of reduced translation is tissue-specific
Longevity
Muscle fecundity/development
Muscle proteotoxicity
Not low translation, per se, that is protective
Heat shock chaperone activation

20. Buck Institute for Research on Aging
Acknowledgements
Lab members
Aric Rogers, Ph.D.
Jarod Rollins, Ph.D.
Noah Lind
Corey Henderson
Former members
Amber Howard, Ph.D.
Bailey Blair
Amruta Valiyaveetil
Sarah Castor
Sarah Dobbins
Isaiah Mansour
Elsie Washburn
Paola Rivera
Charles Allen
Donald Brooks
Collaborators
Nanjing Biomedical Research Institute
Di Chen, Ph.D.
The Jackson Lab
Steve Munger, Ph.D.
University of Hamburg
Zoya Ignatova, Ph.D.
Frauke Adamla, Ph.D.
University of Natural Resources and Life Sicences, Vienna
Markus Schosserer, Ph.D.
Buck Institute for Research on Aging
Pankaj Kapahi, Ph.D.
Funding
The Ellison Medical Foundation
(AG-NS )
National Institute on Aging (R00AG037621)
IDeA from NIGMS of the NIH
(P20GM and P20GM104318)
Other Resources
University of Minnesota
Caenorhabditis Genetics Center
(Funded by NIH ORIP P40 OD010440)

21. Questions?